Contrasting patterns of polymorphism and selection in bacterial‐sensing toll‐like receptor 4 in two house mouse subspecies

Abstract

Detailed investigation of variation in genes involved in pathogen recognition is crucial for understanding co-evolutionary processes between parasites and their hosts. Triggering immediate innate response to invading microbes, Toll-like receptors (TLRs) belong presently among the best-studied receptors of vertebrate immunity. TLRs exhibit remarkable interspecific variation and also intraspecific polymorphism is well documented. In humans and laboratory mice, several studies have recently shown that single amino acid substitution may significantly alter receptor function. Unfortunately, data concerning polymorphism in free-living species are still surprisingly scarce. In this study, we analyzed the polymorphism of Toll-like receptor 4 (Tlr4) over the Palearctic range of house mouse (Mus musculus). Our results reveal contrasting evolutionary patterns between the two recently (0.5 million years ago) diverged house mouse subspecies: M. m. domesticus (Mmd) and M. m. musculus (Mmm). Comparison with cytochrome b indicates strong directional selection in Mmd Tlr4. Throughout the whole Mmd western Palaearctic region, a single variant of the ligand-binding region is spread, encoded mainly by one dominant haplotype (71% of Mmd). In contrast, Tlr4 in Mmm is much more polymorphic with several haplotypes at intermediate frequencies. Moreover, we also found clear signals of recombination between two principal haplogroups in Mmm, and we identified eight sites under positive selection in our dataset. Our results suggest that observed differences in Tlr4 diversity may be attributed to contrasting parasite-mediated selection acting in the two subspecies.

Intensity of infection with intracellular Eimeria spp. and pinworms is reduced in hybrid mice compared to parental subspecies

“…The genetic structure of the MHC and especially polymorphism shared across subspecies should make these loci good candidates to investigate for mechanisms behind hybrid vigour, among a number of other loci including Toll-like receptors (Skevaki, Pararas, Kostelidou, Tsakris, & Routsias, 2015). Previous work on toll-like receptor 4 already suggests different evolutionary patterns between the house mouse subspecies (Fornuskova, Bryja, Vinkler, Macholán, & Piálek, 2014). For host-parasite interactions, major candidate loci are immunity-related GTPases on the host side and rhoptry kinases in coccidia (Lilue, Müller, Steinfeldt, & Howard, 2013).…”

Signatures of diversifying selection and convergence acting on passerine Toll‐like receptor 4 in an evolutionary context

“…TLR4 in particular binds a broad spectrum of structurally diverse ligands including lipopolysaccharides (LPS). It exhibits high levels of putatively adaptive variation, mainly in the ligand-binding region (LBR) that is located in the central part of the ECD (Alcaide & Edwards, 2011;Areal et al, 2011;Forn uskov a, Bryja, Vinkler, Machol an, & Pi alek, 2014;Grueber et al, 2014;Tong et al, 2015;Vinkler, Bryjov a, Albrecht, & Bryja, 2009;Vinkler et al, 2014;Wlasiuk & Nachman, 2010). TLR4 ligand variation is increased by strain-or species-specific modifications such as acylation/de-acylation, phosphorylation or hydroxylation of the LPS in Gram-negative bacteria (Needham & Trent, 2013).…”

Microevolution of bank voles (Myodes glareolus) at neutral and immune-related genes during multiannual dynamic cycles: Consequences for Puumala hantavirus epidemiology

“…Tlr4 is part of Tlrs gene family and is involved in coevolutionary processes with a wide variety of pathogens (Akira et al, 2006;Hughes and Piontkivska, 2008). Several studies recently emphasized the impact of historical and contemporary positive selection on Tlr4 gene polymorphism in rodents (Fornůsková et al, 2014;Fornůsková et al, 2013;Turner et al, 2012), and it is likely that pathogens might mediate this selection. The signature of positive selection observed in this study might reflect spatial heterogeneity in the whole pathogen community or in one/few pathogens recognized by TLR4.…”